1000341-27-4

Usage

Uses

Used in Pharmaceutical Industry:
3-IODO-6-(TRIFLUOROMETHYL) (1H)INDAZOLE is used as a reactant for the preparation of a series of indazole TRPA1 antagonists. These antagonists are important in the development of drugs targeting the transient receptor potential ankyrin 1 (TRPA1) channel, which is involved in various physiological processes, including pain sensation and inflammation. By acting as a reactant in the synthesis of these antagonists, 3-IODO-6-(TRIFLUOROMETHYL) (1H)INDAZOLE plays a crucial role in the development of potential therapeutic agents for conditions such as chronic pain and inflammatory disorders.

Upstream product

• 89763-93-9 2-Fluoro-4-(trifluoromethyl)benzaldehyde 
• 954239-22-6 6-(trifluoromethyl)-1H-indazole 

Downstream Products

• 1204773-05-6 3-phenyl-6-(trifluoromethyl)-1H-indazole 

Relevant academic research and scientific papers

Design, synthesis and structure–activity relationship of indolylindazoles as potent and selective covalent inhibitors of interleukin-2 inducible T-cell kinase (ITK)

Interleukin-2 inducible T-cell kinase (ITK), a member of the Tec family of tyrosine kinases, plays an important role in T cell signaling downstream of the T-cell receptor (TCR). Herein we report the discovery of a series of indolylindazole based covalent ITK inhibitors with nanomolar inhibitory potency against ITK, good kinase selectivity and potent inhibition of the phosphorylation of PLCγ1 and ERK1/2 in living cells. A computational study provided insight into the interactions between inhibitors and Phe437 at the ATP binding pocket of ITK, suggesting that both edge-to-face π-π interaction and the dihedral torsion angle contribute to inhibitors’ potency. Compounds 43 and 55 stood out as selective covalent inhibitors with potent cellular activity, which could be used as chemical tools for further study of ITK functions.

INDAZOLYL-ISOXAZOLE DERIVATIVES FOR THE TREATMENT OF DISEASES SUCH AS CANCER

Compounds of the formula (I) in which R1, R2, X, Y and Z have the meanings indicated in Claim 1, are inhibitors of c-Kit kinase, and can be employed for the treatment of cancer.

Synthesis and Biological Evaluation of 3-Arylindazoles as Selective MEK4 Inhibitors

Herein we report the discovery of a novel series of highly potent and selective mitogen-activated protein kinase kinase 4 (MEK4) inhibitors. MEK4 is an upstream kinase in MAPK signaling pathways that phosphorylates p38 MAPK and JNK in response to mitogenic and cellular stress queues. MEK4 is overexpressed and induces metastasis in advanced prostate cancer lesions. However, the value of MEK4 as an oncology target has not been pharmacologically validated because selective chemical probes targeting MEK4 have not been developed. Optimization of this series via structure–activity relationships and molecular modeling led to the identification of compound 6 ff (4-(6-fluoro-2H-indazol-3-yl)benzoic acid), a highly potent and selective MEK4 inhibitor. This series of inhibitors is the first of its kind in both activity and selectivity and will be useful in further defining the role of MEK4 in prostate and other cancers.

Discovery of a novel 2-(1H-pyrazolo[3,4-b]pyridin-1-yl)thiazole derivative as an EP1 receptor antagonist and in vivo studies in a bone fracture model

We describe a medicinal chemistry approach to the discovery of a novel EP1 antagonist exhibiting high potency and good pharmacokinetics. Our starting point is 1, an EP1 receptor antagonist that exhibits pharmacological efficacy in cystometry models following intravenous administration. Despite its good potency in vitro, the high lipophilicity of 1 is a concern in long-term in vivo studies. Further medicinal chemistry efforts identified 4 as an improved lead compound with good in vitro ADME profile applicable to long term in vivo studies. A rat fracture study was conducted with 4 for 4 weeks to validate its utility in bone fracture healing. The results suggest that this EP1 receptor antagonist stimulates callus formation and thus 4 has potential for enhancing fracture healing.

BICYCLIC NITROGEN-CONTAINING HETEROCYCLIC COMPOUNDS

A nitrogen-containing bicyclic heterocyclic compound represented by the following formula (1) is provided. When the compound or a salt thereof is administered to a human being or an animal, the compound has a strong antagonistic action against EP1 recepto